Kinesin family member2A acts as a potential prognostic marker and treatment target via interaction with PI3K/AKT and RhoA/ROCK pathways in acute myeloid leukemia.

Abstract

KIF2A has been shown to be involved in the regulation of AML pathology, however, the mechanistic role of KIF2A in AML has not been fully identified. The present study aimed to identify the underlying mechanism of KIF2A regulation of AML cell function and chemosensitivity. A total of 58 patients with AML and 30 healthy subjects were enrolled for clinical analysis. AML cells (KG-1 and Kasumi-1) were transfected with KIF2A or control small interfering (si)RNA. PI3K/AKT pathway activator (740 Y-P) and RhoA overexpression plasmid were added to rescue the effect of KIF2A siRNA. Cell proliferation, apoptosis, chemosensitivity to ADR and AraC, expression levels of mRNA/proteins associated with PI3K/AKT and RhoA/ROCK pathways were measured by Cell Counting Kit-8, flow cytometry, reverse transcription-quantitative PCR and western blotting. KIF2A was overexpressed, and correlated with higher levels of bone marrow blast, poor risk classification, lower treatment response and unfavorable survival profile in patients with AML. KIF2A siRNA inhibited proliferation but enhanced apoptosis and chemosensitivity to ADR and AraC in KG-1 and Kasumi-1 cells, which also inactivated PI3K/AKT and RhoA/ROCK pathways. Subsequent rescue experiments showed that 740 Y-P and RhoA overexpression plasmid promoted cell survival and decreased chemosensitivity, which reversed the effect of KIF2A siRNA in KG-1 and Kasumi-1 cells. KIF2A was correlated with worse clinical features and survival in patients with AML; its knockdown promoted apoptosis and chemosensitivity by inactivating PI3K/AKT and RhoA/ROCK signaling pathways in AML cells. These data suggested KIF2A may be a potential prognostic marker and treatment target for AML management.